In addition to the central regulation of the activity of autonomic nerves, some additional modulation also occurs at the peripheral nerve endings by the action of neurotransmitters themselves on prejunctional receptors. It recently has been demonstrated that exogenous adenosine inhibits the release of norepinephrine in response to adrenergic nerve stimulation in some isolated neuroeffector systems. The broad objective of this study is to elucidate the physiological role of endogenous adenosine and related nucleotides in modulating the release of neurotransmitters at peripheral neuroeffector junctions such as heart, salivary gland, vas deferens, etc., and at central adrenergic neurones of hypothalamus and cortex. Adenosine, a coronary dilator, and its metabolic products have been recovered from the perfusate of the heart during hypoxia. Adenosine triphosphate (ATP) and its degraded products appear in the venous effluent after exocytotic release of catecholamines from the adrenal gland. The immediate objective is to determine whether adenosine and its nucleotides modulate the stimulation-induced release of norepinephrine from the sympathetic nerve endings, and the release of catecholamines from the adrenal medulla. If adenosine effectively blocks release, then the mechanism of inhibitory action, together with its interaction with other agents which also influence transmitter release, will be explored. Experiments will be carried out on a number of suitable perfused and superfused neuroeffector organs.